A POTENTIAL MECHANISM OF VASODILATION AFTER WARM HEART-SURGERY - THE TEMPERATURE-DEPENDENT RELEASE OF CYTOKINES

Peripheral vasodilation is a common feature of warm heart surgery and creates clinical concerns when presser agents become necessary because of the potential for some of these drugs to adversely affect flow thr ough newly engrafted arterial and venous bypass conduits. The possible role of a temperature dependent production of cytokines in the pathog enesis of this vasodilation was investigated in a two-part study. In p art I, lipopolysaccharide-activated peritoneal rabbit macrophages (5 x 10(6)/ml) were incubated at 30 degrees or 37 degrees C up to 9 hours and the concentration of tumor necrosis factor released in the superna tant was serially measured by a bioassay. Tumor necrosis factor produc tion was found to increase over time for each of the two temperatures of incubation but was significantly higher throughout the observation period in normothermic experiments than in those done at 30 degrees C. Part II was a prospective clinical study involving 30 patients who un derwent either cold (core temperature 28 degrees to 30 degrees C, n = 15) or warm (37 degrees C, n = 15) cardiopulmonary bypass and in whom serum levels of tumor necrosis factor alpha, interleukin-1 beta, and i nterleukin-6 were measured by enzyme-linked immunosorbent assays at 2, 4, 10, and 24 hours after bypass. Cytokine levels were found to be co nsistently higher in patients having normothermic bypass. Differences between the two groups were significant 2 hours after bypass for tumor necrosis factor alpha and interleukin-6 (p < 0.02 and p = 0.0001, res pectively) and 4 and 10 hours after bypass for interleukin-1 beta (p < 0.01 and p < 0.04, respectively). The incidence of vasodilation neces sitating vasopressor support was twofold higher in the normothermic gr oup (six patients versus three in the hypothermic group). Taken as a w hole, patients supported by presser agents had significantly higher cy tokine levels after bypass than those who did not require presser ther apy. Our results suggest that vasodilation occurring with warm heart o peration is, at least partly, mediated by a temperature-dependent rele ase of cytokines. Vasodilation might therefore be mitigated by simply allowing the core temperature to drift during bypass. Our recent clini cal experience suggests that this ''tepid'' heart surgery (32 degrees to 34 degrees C) effectively blunts most of the vasodilatory response to strictly normothermic bypass without compromising maintenance of my ocardial aerobiosis during arrest.